Oxidative Stress Markers and All-Cause Mortality at Older Age: A Population-Based Cohort Study

Background. The free radical/oxidative stress theory of aging has recently received much attention but the association of oxidative stress markers with all-cause mortality was not yet assessed in humans. Methods. We measured derivatives of reactive oxygen metabolites (d-ROM) as a proxy for the reactive oxygen species concentration and total thiol levels (TTL) as a proxy for the redox control status in 2,932 participants of a population-based cohort study from Germany. Results. The median age of the population was 70 years and 120 (4.1%) study participants died during a mean follow-up of 3.3 years. Compared with the bottom tertiles, the top tertiles of d-ROM and TTL concentrations were both associated with all-cause mortality in models adjusted for age, sex, education, smoking, physical activity, and alcohol consumption (hazard ratios and 95% confidence intervals: 1.63 [1.01; 2.63] and 0.68 [0.53; 0.87], respectively). Adding diseases, the inflammatory marker C-reactive protein or a cumulative somatic morbidity index did not alter the results for TTL. However, the association of d-ROM and mortality was attenuated and no longer statistically significant after adding C-reactive protein and the somatic morbidity index to the model. Conclusions. This study adds epidemiological evidence to the free radical/oxidative stress theory of aging. Both d-ROM and TTL were associated with mortality at older age. For TTL, this association was independent of baseline health status. Inflammation and higher general morbidity could be intermediate states on the pathway from high d-ROM levels to mortality. This hypothesis should to be explored by future studies with repeated measurements.